Current methods of drug and medicinal agent administration include oral, subcutaneous, intradermal, intramuscular, intravenous, intra arterial and transdermal approaches. They share the characteristic that they all utilize distribution via the circulatory system and systemic distribution. With these methods, therapeutic substances that are metabolized by circulatory factors will be rapidly degraded before reaching the target organ or achieving high concentration at the target site. Such methods are also ineffective for the delivery of cells to a specific target organ. For example, when using intravenous and intra arterial administration, the cells may become trapped in nonspecific capillary beds which can result in the failure of a substantial number of the cells from reaching the target site. If a high concentration of any therapeutic substance is required at a specific site, these current methods of drug delivery achieve this therapeutic level for the most part in a nonspecific fashion. As a result, concomitant high concentrations of the therapeutic substance are frequently observed at other organs and sites as well, resulting in undesirable side-effects.
Attempts to circumvent these obstacles by passing catheters in the arterial circulation to the target organ cannot be accomplished when the vessel is occluded from atherosclerosis or if the vessel is too small in caliber. Administration of therapeutic substances in either the arterial or the venous circulation also results in much of the therapeutic agent being lost to the systemic circulation from dilution and potentially rapid degradation. This is an important concern if the target site of therapeutic action is in the interstitial compartment and a high concentration of the therapeutic agent is required for effectiveness. Moreover, the entire organ cannot be visualized or examined directly during administration.
Recent research in growth factors, cellular transplantation, for example, the transplant of mature adult cells, xenograft cells, endo-secretory cells, genetically engineered cells, fetal cells and immune activated cells as well as drugs and immunotherapy, and other medicinal agents, suggest an important role for each of these entities in clinical medicine in the near future. The transition of this research into clinical applications will require an alternative drug delivery system other than the current methods. In particular, these new medicinal agents in some cases need to be administered directly to the tissue or organ which they will affect in order to maximize their medical efficacy and efficiency. The alternative delivery system will need to provide the ability to use direct target organ visualization and examination, allow for very precise delivery of the cells or therapeutic substances at the designated site(s), for example, a target organ in the body of a patient, with minimal systemic distribution and side-effects, and delivery of the cells and substances in high concentrations at the designated site(s), as well as ease of administration and safety for both the patient and the physician.
Growth factors and related substances are expensive, frequently available only in minute quantities and oftentimes are metabolized very rapidly in the systemic circulation. In order for these agents to be used as effective therapeutic agents, they must be delivered to a specific site, often within a very small area, at the target organ. The level of concentration of the growth factor and related substances must be high to be effective. Contact with the circulatory system must be minimal to avoid rapid degradation and dilution.
Another current approach using percutaneous single needle puncture guided by fluoroscopy, computer tomography scan or ultrasound is used primarily for diagnostic and drainage procedures. Many potential target organs are inaccessible by this approach. Localization is not precise enough and it does not provide for direct visualization and examination of the target organ. Furthermore, complications, such as bleeding, cannot be observed during the procedure.
Convergent with the above mentioned research is the rapid development of minimally invasive surgery. Prior to this, any direct visualization and examination of internal organs are performed through a formal operation. This is associated with pain and discomfort for the patient, potential complications, hospitalization and a variable period of convalescence. With minimally invasive surgery, the operative procedure is performed through three small "keyhole" incisions using special surgical instruments and endoscopic techniques and equipment. With the utilization of fiber optics and a monitor, the minimally invasive surgical approach can provide direct visualization and examination of organs in the abdomen, chest and elsewhere. Moreover, it is accomplished with minimal pain and discomfort to the patient. The patient is sometimes discharged as early as the day of the operation. The period of convalescence is short. At the present time, minimally invasive procedures are used for diagnosis and for treatment of diseases treated previously with conventional surgical procedures.